Fenfluramine anorexia: a peripheral locus of action

In a series of feeding pattern studies, amphetamine was shown to produce a period of complete anorexia often followed by a broken nibbling pattern of eating. Fenfluramine produced a regular feeding pattern in which a depressed meal size was not compensated for by an increase in meal frequency. The disproportionate lengthening of the post-meal interval relative to meal size was accompanied by a decrease in the rate of gastric emptying. Fenfluramine was most effective in lengthening post-meal interval when administered immediately after a meal, and was progressively less effective when the injection was delayed, allowing time for gastric emptying to occur. Amphetamine was shown to have similar but less pronounced effects, corresponding to its weaker effects on gastric emptying. Midbrain raphe lesions that abolished the fenfluramine effect on short-term intake of food-deprived rats did not attenuate fenfluramine's effect on gastric emptying, nor did the lesions attenuate the anorectic effect of fenfluramine on ad lib food intake. Lateral intracerebroventricular administration of fenfluramine not reduce feeding. These results suggest that fenfluramine controls feeding primarily by short-term signals related to food in the upper gastro-intestinal tract.